Serological identification and molecular characterization of B (A) 02 subtype in patients and blood donors from Eastern China

This study was designed to identify the rare?type?ABO?blood?groups, B(A) 02, from Eastern China. Three samples with discordant serological results during routine blood type identification and four samples from one sample’ family were selected. All of them were detected by serological method. The exon 6 and 7 of the ABO genes were amplified by PCR and sequenced. They were typed as AsubB by serology and as BO by genotype. In AsubB samples, nt 700C>G mutation was detected in B gene, which was previously defined as B(A)02 alleles. In these seven samples, six showed B(A)02/O01 and one showed B(A)02/O02.B(A)02 allele was found to be more common in this study than B(A)04 which is considered to be more frequent than B(A)02. The careful identification of rare blood types is important for the safety of clinical blood transfusion.     

A Mechanism for Ultra-Slow Oscillations in the Cortical Default Network

When the brain is in its noncognitive “idling” state, functional MRI measurements reveal the activation of default cortical networks whose activity is suppressed during cognitive processing. This default or background mode is characterized by ultra-slow BOLD oscillations (∼0.05 Hz), signaling extremely slow cycling in cortical metabolic demand across distinct cortical regions. Here we describe a model of the cortex which predicts that slow cycling of cortical activity can arise naturally as a result of nonlinear interactions between temporal (Hopf) and spatial (Turing) instabilities. The Hopf instability is triggered by delays in the inhibitory postsynaptic response, while the Turing instability is precipitated by increases in the strength of the gap-junction coupling between interneurons. We comment on possible implications for slow dendritic computation and information processing.     

A decade of atrial fibrillation ablation

Background

Over the past decade, radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) has evolved into a frequently performed procedure. The aim of this study was to monitor changes in patient characteristics, procedural characteristics, outcomes and complications over the past 10 years.

Methods

All consecutive patients who underwent primary RFCA treatment of AF in the University Medical Center Utrecht from 2005–2015 were included. In all patients, the primary ablation strategy was pulmonary vein (PV) antrum isolation without additional substrate modification. Baseline patient and procedure characteristics, and 1?year follow-up data of 975 patients were prospectively collected.

Results

In 2005, 73.4% of patients suffered from paroxysmal AF, which decreased to 45.3% in 2014. Mean age increased from 54 ± 9 to 61 ± 10 years and CHA₂DS₂-VASc score ≥2 from 18 to 40.6%. History of AF decreased significantly from 7 to 4 years. Mean procedure duration was 237 ± 53?min in 2005 and 163 ± 41?min in 2014. Fluoroscopy time significantly decreased from 41 ± 17 to 19 ± 8?min and total radiation exposure from 465 (263–687) to 210 (118–376) mGy. One-year success remained similar (2005: 55.6%, 2014: 54.8%), as did the amount of PV reconnection observed during redo procedures. Due to a marked reduction in vascular complications and moderate PV stenosis, the total complication rate decreased significantly.

Conclusion

Over the past decade, AF ablation has increasingly been performed in older patients with persistent AF and more comorbidity. Moreover, it has been performed earlier after AF diagnosis. Although several performance parameters, such as procedure duration and complication rate, improved, 1?year single procedure success remained unchanged.

     

A genome-wide analysis of the expansin genes in Malus × Domestica

Expansins were first identified as cell wall-loosening proteins; they are involved in regulating cell expansion, fruits softening and many other physiological processes. However, our knowledge about the expansin family members and their evolutionary relationships in fruit trees, such as apple, is limited. In this study, we identified 41 members of the expansin gene family in the genome of apple (Malus × Domestica L. Borkh). Phylogenetic analysis revealed that expansin genes in apple could be divided into four subfamilies according to their gene structures and protein motifs. By phylogenetic analysis of the expansins in five plants (Arabidopsis, rice, poplar, grape and apple), the expansins were divided into 17 subgroups. Our gene duplication analysis revealed that whole-genome and chromosomal-segment duplications contributed to the expansion of Mdexpansins. The microarray and expressed sequence tag (EST) data showed that 34 Mdexpansin genes could be divided into five groups by the EST analysis; they may also play different roles during fruit development. An expression model for MdEXPA16 and MdEXPA20 showed their potential role in developing fruit. Overall, our study provides useful data and novel insights into the functions and regulatory mechanisms of the expansin genes in apple, as well as their evolution and divergence. As the first step towards genome-wide analysis of the expansin genes in apple, our results have established a solid foundation for future studies on the function of the expansin genes in fruit development.     

The Role of Viral Infection in Pest Control: A Mathematical Study

In this paper, we propose a mathematical model of viral infection in pest control. As the viral infection induces host lysis which releases more virus into the environment, on the average ‘κ’ viruses per host, κ∈(1,∞), so the ‘virus replication parameter’ is chosen as the main parameter on which the dynamics of the infection depends. There exists a threshold value κ ₀ beyond which the infection persists in the system. Still for increasing the value of κ, the endemic equilibrium bifurcates towards a periodic solution, which essentially indicates that the viral pesticide has a density-dependent ‘numerical response’ component to its action. Investigation also includes the dependence of the process on predation of natural enemy into the system. A concluding discussion with numerical simulation of the model is also presented.     

A New Method of Assessing Lipid Mixtures by 31P Magic-Angle Spinning NMR

A variety of lipids that differ by their chains and headgroups are found in biomembranes. In addition to studying the overall membrane phase, determination of the structure, dynamics, and headgroup conformation of individual lipids in the mixture would be of great interest. We have thus developed, to our knowledge, a new approach using solid-state ³¹P NMR, magic-angle spinning, and chemical-shift anisotropy (CSA) recoupling, using an altered version of the recoupling of chemical shift anisotropy (ROCSA) pulse sequence, here penned PROCSA. The resulting two-dimensional spectra allowed the simultaneous measurement of the isotropic chemical shift and CSA of each lipid headgroup, thus providing a valuable measure of its dynamics and structure. PROCSA was applied to mixtures of phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) in various relative proportions, to mimic bacterial membranes and assess the respective roles of lipids in shaping these bilayers. The results were interpreted in terms of membrane topology, lipid propensity to adopt various phases or conformations, and lipid-lipid miscibility. Our results showed that PG dictates the lipid behavior when present in a proportion of 20 mol % or more. A small proportion of PG is thus able to impose a bilayer structure to the hexagonal phase forming PE. We discuss the requirement for lipids, such as PE, to be able to adopt non-bilayer phases in a membrane.     

Methanol Accelerates DMPC Flip-Flop and Transfer: A SANS Study on Lipid Dynamics

Methanol is a common solubilizing agent used to study transmembrane proteins/peptides in biological and synthetic membranes. Using small angle neutron scattering and a strategic contrast-matching scheme, we show that methanol has a major impact on lipid dynamics. Under increasing methanol concentrations, isotopically distinct 1,2-dimyristoyl-sn-glycero-3-phosphocholine large unilamellar vesicle populations exhibit increased mixing. Specifically, 1,2-dimyristoyl-sn-glycero-3-phosphocholine transfer and flip-flop kinetics display linear and exponential rate enhancements, respectively. Ultimately, methanol is capable of influencing the structure-function relationship associated with bilayer composition (e.g., lipid asymmetry). The use of methanol as a carrier solvent, despite better simulating some biological conditions (e.g., antimicrobial attack), can help misconstrue lipid scrambling as the action of proteins or peptides, when in actuality it is a combination of solvent and biological agent. As bilayer compositional stability is crucial to cell survival and protein reconstitution, these results highlight the importance of methanol, and solvents in general, in biomembrane and proteolipid studies.     

A clinical approach to arrhythmias revisited in 2018

Understanding arrhythmias and their treatment is not always easy. The current straightforward approach with catheter ablation and device therapy is an amazing achievement, but does not make management of underlying or other cardiac disease and pharmacological therapy unnecessary. The goal of this paper is to describe how much of the knowledge of the 1980s and early 1990s can and should still be applied in the modern treatment of patients with arrhythmias. After an introduction, this review will focus on paroxysmal atrial fibrillation and a prototype of ‘idiopathic’ ventricular arrhythmias, two diseases with a striking similarity, and will discuss the arrhythmogenesis. The ECG continues to play an important role in diagnostics. Both diseases are associated with a structurally normal heart; the autonomic nervous system plays an important role in triggering arrhythmias at both the atrial and ventricular level.     

A middleware approach for pipelining communications in clusters

The Pipelining Communications Middleware (PCM) approach provides a flexible, simple, high-performance mechanism to connect parallel programs running on high performance computers or clusters. This approach enables parallel programs to communicate and coordinate with each other to address larger problems than a single program can solve. The motivation behind the PCM approach grew out of using files as an intermediate transfer stage between processing by different programs. Our approach supersedes this practice by using streaming data set transfers as an “online” communication channel between simultaneously active parallel programs. Thus, the PCM approach addresses the issue of sending data from a parallel program to another parallel program without exposing details such as number of nodes allocated to the program, specific node identifiers, etc. This paper outlines and analyzes our proposed computation and communication model to provide efficient and convenient communications between parallel programs running on high performance computing systems or clusters. We also discuss the PCM challenges as well as current PCM implementations. Our approach achieves scalability, transparency, coordination, synchronization and flow control, and efficient programming. We experimented with data parallel applications to evaluate the performance of the PCM approach. Our experiment results show that the PCM approach achieves nearly ideal throughput that scales linearly with the underlying network medium speed. PCM performs well with small and large data transfers. Furthermore, our experiments show that network infrastructure plays the most significant role in the PCM performance.

A general mathematical performance model for wormhole-switched irregular networks

Irregular topologies are desirable network structures for building scalable cluster systems and very recently they have also been employed in SoC (system-on-chip) design. Many analytical models have been proposed in the literature to evaluate the performance of networks with different topologies such as hypercube, torus, mesh, hypermesh, Cartesian product networks, star graph, and k-ary n-cube; however, to the best of our knowledge, no mathematical model has been presented for irregular networks. Therefore, as an effort to fill this gap, this paper presents a comprehensive mathematical model for fully adaptive routing in wormhole-switched irregular networks. Moreover, since our approach holds no assumption for the network topology, the proposed analytical model covers all the aforementioned models (i.e. it covers both regular and irregular topologies). Furthermore, the model makes no preliminary assumption about the deadlock-free routing algorithm applied to the network. Finally, besides the generality of the model regarding the topology and routing algorithm, our analysis shows that the analytical model exhibits high accuracy which enables it to be used for almost all topologies with all traffic loads.     

Impacts of Incubation Delay on the Dynamics of an Eco-Epidemiological System—A Theoretical Study

Parasite and predator play significant role in trophic interaction, productivity and stability of an ecosystem. In this paper, we have studied a host-parasite-predator interaction that incorporates incubation delay. How the qualitative and quantitative behaviors of the system alter with the incubation delay have been discussed both from mathematical and biological point of views. It is observed that for a lower infection rate, the system is stable for all delays; but for a higher infection rate, there exists a threshold value of the delay above which the system is unstable and below which the system is stable leading to the persistence of all the species. Also, the instability arising from the incubation delay may be controlled if somehow the growth rate of predator population is increased. Numerical studies have also been performed to illustrate different analytical findings. Research is supported by UGC, India; F No. 32-173/2006(SR).     

Gigantonoclea guizhouensis Gu et Zhi 的叶部解剖研究

一、材料来源和研究方法解剖研究所用的D-1标本是笔者于1984年5月在贵州水城大河边煤矿二采区新开辟的运输巷侧壁砂岩中采到的,其层位经对比与田宝霖和张连武(1980)描述的水城汪家寨矿区综合地层柱中龙潭组下部第8分层的中部砂岩相当。该叶片沉积时受水流冲击,以中脉为对称轴向远轴侧对折成约20°角状(图版Ⅰ,图2)。     

Tailoring Proteins to Re-Evolve Nature: A Short Review

Proteins are key biomolecules for most biological processes, their function is related to their conformation that is also dictated by their sequence of amino acids. Through evolution, nature has produced an immense variety of enzymatic tools of high efficiency and selectivity, and thanks to the understanding of the molecular basis of life and the technological advances, scientists have learned to introduce mutations and select mutant enzymes, to optimize and control their molecular fitness characteristics mainly for industrial, medical and environmental applications. The relationship between protein structure and enzymatic functionality is essential, and there are various experimental and instrumental techniques for unravelling the molecular changes, activities and specificities. Protein engineering applies computational tools, in hand with experimental tools for mutations, like directed evolution and rational design, along with screening methods to obtain protein variations with the desired properties under a short time frame. With innovations in technology, it is possible to fine tune properties in proteins and reach new frontiers in their applications. The present review will briefly discuss these points and methods, with a glimpse on their strengths and pitfalls, while giving an overview of the versatility of synthetic proteins and their huge potential for biotechnological and biomedical fields.     

A Geometric Buildup Algorithm for the Solution of the Distance Geometry Problem Using Least-Squares Approximation

We propose a new geometric buildup algorithm for the solution of the distance geometry problem in protein modeling, which can prevent the accumulation of the rounding errors in the buildup calculations successfully and also tolerate small errors in given distances. In this algorithm, we use all instead of a subset of available distances for the determination of each unknown atom and obtain the position of the atom by using a least-squares approximation instead of an exact solution to the system of distance equations. We show that the least-squares approximation can be obtained by using a special singular value decomposition method, which not only tolerates and minimizes small distance errors, but also prevents the rounding errors from propagation effectively, especially when the distance data is sparse. We describe the least-squares formulations and their solution methods, and present the test results from applying the new algorithm for the determination of a set of protein structures with varying degrees of availability and accuracy of the distances. We show that the new development of the algorithm increases the modeling ability, and improves stability and robustness of the geometric buildup approach significantly from both theoretical and practical points of view.     

Ly49A allelic variation and MHC class I specificity

The Ly49 family of natural killer (NK) cell receptors is encoded by a polygenic genetic locus. Allelic forms have been described and their expression appears to be regulated. The best-characterized Ly49 molecule, the C57BL/6 form of Ly49A, is an NK cell inhibitory receptor that binds H2Dd. To determine whether differences between Ly49a alleles may have functional consequences, allelic variants of Ly49a were cloned from several inbred mouse strains. Stable transfectants expressing each Ly49a allelic variant were generated and tested for reactivity with a panel of monoclonal antibodies (mAbs A1, JR9.318, YE1/32, and YE1/48) that recognize the C57BL/6 form of Ly49A. Binding to H2Dd was also assessed using fluorescently labeled H2Dd tetramers. Furthermore, cytotoxicity assays were performed using anti-Ly49A mAb-separated interleukin-2-activated NK cells. We show that despite binding to fluorescently labeled H2Dd tetramers, the Ly49A+ NK cells from representative mouse strains displayed significantly different degrees of inhibition with H2Dd targets. These results can be interpreted in the light of recent structural data on the Ly49A-H2Dd complex. Thus, the Ly49 family displays functionally significant allelic polymorphism which adds to the repertoire of NK cell receptors.     

A regression-based analytic model for capacity planning of multi-tier applications

The multi-tier implementation has become the industry standard for developing scalable client-server enterprise applications. Since these applications are performance sensitive, effective models for dynamic resource provisioning and for delivering quality of service to these applications become critical. Workloads in such environments are characterized by client sessions of interdependent requests with changing transaction mix and load over time, making model adaptivity to the observed workload changes a critical requirement for model effectiveness. In this work, we apply a regression-based approximation of the CPU demand of client transactions on a given hardware. Then, we use this approximation in an analytic model of a simple network of queues, each queue representing a tier, and show the approximation’s effectiveness for modeling diverse workloads with a changing transaction mix over time. Using two case studies, we investigate factors that impact the efficiency and accuracy of the proposed performance prediction models. Experimental results show that this regression-based approach provides a simple and powerful solution for efficient capacity planning and resource provisioning of multi-tier applications under changing workload conditions.

Interaction of Tumor with Its Micro-environment: A Mathematical Model

This paper is concerned with early development of transformed epithelial cells (TECs) in the presence of fibroblasts in the tumor micro-environment. These two types of cells interact by means of cytokines such as transforming growth factor (TGF-β) and epidermal growth factor (EGF) secreted, respectively, by the TECs and the fibroblasts. As this interaction proceeds, TGF-β induces fibroblasts to differentiate into myofibroblasts which secrete EGF at a larger rate than fibroblasts. We monitor the entire process in silico, in a setup which mimics experiments in a Tumor Chamber Invasion Assay, where a semi-permeable membrane coated by extracellular matrix (ECM) is placed between two chambers, one containing TECs and another containing fibroblasts. We develop a mathematical model, based on a system of PDEs, that includes the interaction between TECs, fibroblasts, myofibroblasts, TGF-β, and EGF, and we show how model parameters affect tumor progression. The model is used to generate several hypotheses on how to slow tumor growth and invasion. In an Appendix, it is proved that the mathematical model has a unique global in-time solution.     

Highly Efficient Protein-free Membrane Fusion: A Giant Vesicle Study

Membrane fusion is a ubiquitous process in biology and is a prerequisite for many intracellular delivery protocols relying on the use of liposomes as drug carriers. Here, we investigate in detail the process of membrane fusion and the role of opposite charges in a protein-free lipid system based on cationic liposomes (LUVs, large unilamellar vesicles) and anionic giant unilamellar vesicles (GUVs) composed of different palmitoyloleoylphosphatidylcholine (POPC)/palmitoyloleoylphosphatidylglycerol (POPG) molar ratios. By using a set of optical-microscopy- and microfluidics-based methods, we show that liposomes strongly dock to GUVs of pure POPC or low POPG fraction (up to 10 mol%) in a process mainly associated with hemifusion and membrane tension increase, commonly leading to GUV rupture. On the other hand, docked LUVs quickly and very efficiently fuse with negative GUVs of POPG fractions at or above 20 mol%, resulting in dramatic GUV area increase in a charge-dependent manner; the vesicle area increase is deduced from GUV electrodeformation. Importantly, both hemifusion and full fusion are leakage-free. Fusion efficiency is quantified by the lipid transfer from liposomes to GUVs using fluorescence resonance energy transfer (FRET), which leads to consistent results when compared to fluorescence-lifetime-based FRET. We develop an approach to deduce the final composition of single GUVs after fusion based on the FRET efficiency. The results suggest that fusion is driven by membrane charge and appears to proceed up to charge neutralization of the acceptor GUV.